Biology subjects

Xenarios, I.

Publications and source records attributed to Xenarios, I..

4 recordsLinked to original sources

bioRxiv2018

Estimating the Contribution of Proteasomal Spliced Peptides to the HLA-I Ligandome

Spliced peptides are short protein fragments spliced together in the proteasome by peptide bond formation. True estimation of the contribution of proteasome-spliced peptides (PSPs) to the global Human Leukocyte Antigen (HLA) ligandome is critical. A recent study suggested that PSPs contribute up to 30% of the HLA ligandome. We performed a thorough reanalysis of the reported results using multiple computational tools and various validation steps and concluded that only a fraction of the proposed PSPs passes the quality filters. To better estimate the actual number of PSPs, we present an alternative workflow. We performed de-novo sequencing of the HLA-peptide spectra and discarded all de-novo sequences found in the UniProt database. We checked whether the remaining de-novo sequences could match spliced peptides from human proteins. The spliced sequences were appended to the UniProt fasta file, which was searched by two search tools at a FDR of 1%. We find that maximally 2-4% of the HLA ligandome could be explained as spliced protein fragments. The majority of these potential PSPs have good peptide-spectrum match properties and are predicted to bind the respective HLA molecules. However, it remains to be shown how many of these potential PSPs actually originate from proteasomal splicing events.

bioinformatics↗

bioRxiv2018

Navigating in vitro bioactivity data: investigating available resources using model compounds

Modern medicine and an increasingly complex environment contribute to exposure of humans to a large number of chemical compounds, that can potentially be toxic. Although widely used, compound testing in animals has important limitations. In vitro testing provides a promising alternative. However, because of the relative inaccessibility and fragmentation of available data, the in vitro approach largely underperforms its potential. The aim of this study is to investigate how available public online resources (tools and databases) support accessing and distribution of in vitro compound data. We examined 19 public online resources, mapped their features, and evaluated their usability with a set of four model compounds (aspirin, rosiglitazone, valproic acid, and tamoxifen). By investigating compound names and identifiers, we observed extensive variation and inconsistencies in available resources: the synonyms were different, compounds structural identifiers (InChI, InChIKey, SMILES and IUPAC systematic name) underperformed in omics databases, identification of compound related metadata (e.g. concentrations used in the experiments) from omics experiments was complex and none of the available resources clearly distinguished between in vivo and in vitro data. In addition, we estimated accessibility of selected public resources using computational queries. Only a few public resources provided access to compound-related data using semantic web technology. The general quality of experiment annotations created further difficulties in identifying data of interest. Therefore, we identified several standardized ontologies with potential to provide an increased accuracy for extensive data retrieval of in vitro compound data. Furthermore, using the examples of our model compounds, we provide recommendations on the use of ontologies by suggesting specific ontology terms to annotate in vitro experimental data when being published.

pharmacology and toxicology↗

bioRxiv2017

Taxon sampling unequally affects individual nodes in a phylogenetic tree: consequences for model gene tree construction in SwissTree

Medium to large phylogenetic gene trees constructed from datasets of different species density and taxonomic range are rarely topologically consistent because of missing phylogenetic signal, non-phylogenetic signal and error. In this study, we first use simulations to show that taxon sampling unequally affects nodes in a gene tree, which likely contributes to controversial conclusions from taxon sampling experiments and contradicting species phylogenies such as for the boreoeutherians. Hence, because it is unlikely that a large gene tree can be reconstructed correctly based on a single optimized dataset, we take a two-step approach for the construction of model gene trees. First, stable and unstable clades are identified by comparing phylogenetic trees inferred from multiple datasets and data types (nucleotide, amino acid, codon) from the same gene family. Subsequently, data subsets are optimized for the analysis of individual uncertain clades. Results are summarized in form of a model tree that illustrates the evolutionary relationship of gene loci. A case study shows how a seemingly complex gene phylogeny becomes increasingly consistent with the reference species tree by attentive taxon sampling and subtree analysis. The procedure is progressively introduced to SwissTree (http://swisstree.vital-it.ch), a resource of high confidence model gene (locus) trees. Finally we demonstrate the usefulness of SwissTree for orthology benchmarking.

bioinformatics↗

bioRxiv2017

Low Rate of Somatic Mutations in a Long-Lived Oak Tree

Because plants do not possess a proper germline, deleterious somatic mutations can be passed to gametes and a large number of cell divisions separating zygote from gamete formation in long-lived plants may lead to many mutations. We sequenced the genome of two terminal branches of a 234-year-old oak tree and found few fixed somatic single-nucleotide variants (SNVs), whose sequential appearance in the tree could be traced along nested sectors of younger branches. Our data suggest that stem cells of shoot meristems are robustly protected from accumulation of mutations in trees.

plant biology↗